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Single-Dose, Therapeutic Vaccination of Mice with Vesicular Stomatitis Virus Expressing Human Papillomavirus Type 16 E7 Protein

John B. Liao,^1,2, Jean Publicover,³ John K. Rose,⁴ and Daniel DiMaio^5*

Department of Obstetrics, Gynecology, and Reproductive Sciences,¹ Investigative Medicine Program,² Microbiology Graduate Program,³ Department of Pathology,⁴ Departments of Genetics, Molecular Biophysics and Biochemistry, and Therapeutic Radiology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510⁵

Received 21 August 2007/ Returned for modification 20 November 2007/ Accepted 12 February 2008

We are developing recombinant attenuated vesicular stomatitis virus (VSV) as a vaccine vector to generate humoral and cell-mediated immune responses. Here, we explore the use of VSV vaccines for cancer immunotherapy. Immunotherapy targeting high-risk human papillomavirus (HPV) lesions has the potential to benefit HPV-infected individuals and cervical cancer patients by generating cytotoxic T cells that kill tumor cells that express viral antigens. A single dose of VSV expressing the HPV type 16 (HPV16) E7 oncogene was used for therapeutic vaccination of mice bearing TC-1 syngeneic tumors, which express HPV16 E7. HPV16 E7-specific T cells were generated and displayed cytotoxic activity against the tumor cells. By 14 days postvaccination, average tumor volumes were 10-fold less in the vaccinated group than in mice that received the empty-vector VSV, and regression of preexisting tumors occurred in some cases. This antitumor effect was CD8 T-cell dependent. Our results demonstrate antitumor responses to HPV16 E7 and suggest that recombinant-VSV-based vaccination should be explored as a therapeutic strategy for cervical carcinoma and other HPV-associated cancers.

Published ahead of print on 12 March 2008.

Present address: Department of Ob/Gyn, University of Pennsylvania, 421 Curie Blvd., Philadelphia, PA 19104.